D14-b - Lignin Composites Impact Fibroblast and Immune Cell Populations to Promote Diabetic Wound Healing

Saturday, October 11, 2025

10:00 AM - 12:00 PM PDT

Location: Exhibit Hall F, G & H

Presenting Author(s)

Anthony You

Research Intern
Laboratory for Regenerative Tissue Repair, Department of Pediatric Surgery, Baylor college of Medicine and Texas Children's Hospital., United States

Co-Author(s)

Varun Akondy, n/a

Research Intern
Laboratory for Regenerative Tissue Repair, Department of Pediatric Surgery, Baylor college of Medicine and Texas Children's Hospital.
Cypress, Texas, United States
Feteme Nazaryabrbekoh

Research Assistant
Louisiana State University, Department of Biological Engineering
Baton Rouge, Louisiana, United States
RC

Rami A. Choumar

Research Assistant
Louisiana State University, Department of Biological Engineering, United States
AK

Arin Kumar

Research Intern
Laboratory for Regenerative Tissue Repair, Department of Pediatric Surgery, Baylor college of Medicine and Texas Children’s Hospital., United States
TL

Taylor Lee

Research Assistant
Laboratory for Regenerative Tissue Repair, Department of Pediatric Surgery, Baylor college of Medicine and Texas Children’s Hospital., United States
VW

Vincent Wollner

Research Intern
Laboratory for Regenerative Tissue Repair, Department of Pediatric Surgery, Baylor college of Medicine and Texas Children’s Hospital., United States
ZC

Zara Chandrasekhar

Research Intern
Laboratory for Regenerative Tissue Repair, Department of Pediatric Surgery, Baylor college of Medicine and Texas Children’s Hospital., United States
ML

Mary Hui Li

Research Scientist
Laboratory for Regenerative Tissue Repair, Department of Pediatric Surgery, Baylor college of Medicine and Texas Children’s Hospital., United States
Ling Yu, PhD

Research Scientist
Laboratory for Regenerative Tissue Repair, Department of Pediatric Surgery, Baylor college of Medicine and Texas Children’s Hospital., United States
Mary Elizabeth Guerra, MD

Research Assistant
Laboratory for Regenerative Tissue Repair, Department of Pediatric Surgery, Baylor college of Medicine and Texas Children’s Hospital., United States
Jangwook P. Jung, PhD

Associate Professor
Louisiana State University
Baton Rouge, Louisiana, United States
Swathi Balaji, PhD

Associate Professor
Laboratory for Regenerative Tissue Repair, Department of Pediatric Surgery, Baylor college of Medicine and Texas Children’s Hospital.
Houston, Texas, United States
CB

Casey Baxter

Research Assistant
Laboratory for Regenerative Tissue Repair, Department of Pediatric Surgery, Baylor college of Medicine and Texas Children’s Hospital., United States

Introduction: : Chronic diabetic wounds are a major healthcare burden. Impaired healing in the diabetic environment is characterized by ischemia, excessive reactive oxygen species (ROS), inflammation and poor neovascularization. We engineered novel lignin (a natural antioxidant from lignocellulose)-based composites that scavenge ROS and produce oxygen. In a diabetic mouse model, these composites promoted faster wound closure, enhanced granulation tissue formation, increased neovascularization, and reduced inflammation. However, the specific cellular mechanisms of this improved healing remain unknown. We hypothesize that these composites, specifically as lignin nanoparticles, promote wound repair by directly affecting and driving distinct subpopulations of dermal fibroblasts and macrophages, key cellular mediators of tissue remodeling and inflammation.

Materials and

Methods: : Excisional 6 mm stented wounds in db/db(type II diabetic) mice were treated with lignin composites. We evaluated four groups: an untreated control (UNTX), a GelMA hydrogel with thiolated lignosulfonate (TLS) antioxidant nanoparticles, the full composite GelMA+TLS+CPO with oxygen-generating nanoparticles, and a control composite GelMA+TLS+CPOc that lacked oxygen generation. At days 7 and 14, wounds were harvested for 10x Visium Spatial Transcriptomics RNA sequencing. We used Cell2location workflows to analyze gene expression, ensuring data quality through rigorous checkpoints and comparisons with reference repositories. We included three biological replicates per group (n=3).

Results, Conclusions, and Discussions:: Full thickness wounds in db/db mice treated with GelMA+TLS+CPO lignin composites demonstrated faster healing and robust granulation tissue deposition that persisted through D14. 10x Visium spatial transcriptomics showed that lignin composites uniquely influenced the spatial distribution of immune and fibroblast cell populations within the wound. Specifically, D7 wounds treated with the dual functioning nanoparticles (GelMA+TLS+CPO) wounds showed a distinct gene expression signature, with decreased fibroblast and increased smooth muscle tissue signatures (Fig. 1) compared to UNTX wounds..
The dual functioning nanoparticle composites impact fibroblasts by downregulating profibrotic genes, which uniquely alters their phenotype and geospatial distribution within wounds. These data provide a novel mechanistic basis for the lignin nanoparticles’ healing effect and supports their development as an effective biomaterial to facilitate improved healing.

Acknowledgements and/or References (Optional): : N/A